Lec12_Influenza

Lec12_Influenza - Influenza Influenza Influenza A virus is...

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Influenza
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Influenza Influenza A virus is the only agent which causes annual epidemics   of disease with attack rates of 10–40% over a six-week period Historically it has caused pandemics with millions of deaths worldwide In U.S., there are 10,000 to 40,000 excess deaths per year and about 200,000 hospitalizations are attributed to annual influenza epidemics Epidemics occur despite an effective vaccine and antiviral drugs Influenza A virus is a highly mutable virus with frequent antigenic drift and occasional antigenic shift
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Influenza
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Influenza Influenza viruses have three levels of nomenclature 1. Type—influenza "A, B, or C” 2. Subtype—specific HA, NA: influenza A "H3N2” (defines major surface antigens) 3. Strain—specific site and year of isolation: "A/Victoria/75 (H3N2)” (defines specific minor antigens)
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Influenza Influenza virus is a Myxovirus belonging to the family Orthomyxoviridae. Parainfluenza viruses, mumps, measles and respiratory syncytial virus are members of the Paramyxovirus family. All these viruses cause respiratory symptoms as part of their clinical picture.
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Influenza
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Influenza Source: Webster RG. Virology. A Molecular Whodunit. Science 2001;293: 1773.
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Influenza RNA segment number Gene production description Name of protein Proposed functions of protein 1 PB1 Polymerase RNA transcriptase 2 PB Polymerase RNA transcriptase, virulence 3 PA Polymerase RNA transcriptase 4 HA Hemagglutinin Attachment to cell membranes; major antigenic determinant 5 NA Neuraminidase Release from membranes; major antigenic determinant 6 NP Nucleoprotein Encapsidates RNA 7 M Matrix Surrounds viral core; involved in assembly and budding 8 –NS1 –NS2 – Nonstructural – Nonstructural – RNA binding, interferon antagonist – Unknown
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Adapted from Levine AJ . Viruses. 1992;165, with permission. Hemagglutinin Subtypes of Influenza A Virus Subtype Human Swine Horse Bird H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15
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Adapted from Levine AJ . Viruses. 1992;165, with permission . Hemagglutinin Subtypes of Influenza A Virus Subtype Human Swine Horse Bird H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15
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Adapted from Levine AJ . Viruses. 1992;165, with permission . Neuraminidase Subtypes of Influenza A Virus Subtype Human Swine Horse Bird N1 N2 N3 N4 N5 N6 N7 N8 N9
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Adapted from Levine AJ . Viruses. 1992;165, with permission . Neuraminidase Subtypes of Influenza A Virus Subtype Human Swine Horse Bird N1 N2 N3 N4 N5 N6 N7 N8 N9
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Influenza The 15 HA and 9 NA subtypes are widely distributed in nature, though they clearly favor GI tract of aquatic birds. It is thought that feral and domestic fowl are the natural host, with stable adaptation, little disease.
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Influenza Influenza viruses have a high rate of viral mutability RNA genome viruses have high rate of spontaneous mutation: 10 3 to 10 6 /incorporated nucleotide This equates to about 1 base substitution in the HA gene per viral generation, which generates an “exploration” of all variations of amino acid sequence
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